Abstract
Background:
Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is caused by germ line mutations in the PTEN gene. Symptoms include cancer predisposition, immune deviations, and lipomas/lipomatosis. No causal standard therapy is available. We describe a therapeutic attempt with the mammalian target of rapamycin (mTOR) inhibitor sirolimus for a PHTS patient suffering from thymus hyperplasia and lipomatosis. We furthermore assessed the in vitro effects of sirolimus and other inhibitors on lipoma cells of the patient.
Methods:
The patient underwent clinical and blood examinations and whole-body magnetic resonance imaging to assess tumor sizes. Lipoma cells of the patient were incubated with inhibitors of the phosphoinositide-3-kinase (PI3K)/AKT/mTOR signaling pathway to analyze the effects on proliferation, adipocyte differentiation, and survival in vitro.
Results:
Sirolimus treatment improved somatic growth and reduced thymus volume. These effects diminished over the treatment period of 19 mo. Sirolimus decreased lipoma cell proliferation and adipocyte differentiation in vitro but did not cause apoptosis. PI3K and AKT inhibitors induced apoptosis significantly.
Conclusion:
Sirolimus treatment led to an improvement of the patient’s clinical status and a transient reduction of the thymus. Our in vitro findings point to PI3K and AKT inhibitors as potential treatment options for patients with severe forms of PHTS.
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Acknowledgements
We are grateful to the family of the reported patient for supporting our work and to his physicians and the nurses who help to care for the patient in the hospital and outpatient clinics. We also thank our technical assistants Antje Berthold, Roy Tauscher, Anja Barnikol-Oettler, and Sandy Laue for excellent work, Lars-Christian Horn for advice on histology, and our colleagues from the Center for Pediatric Research for helpful discussions.
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Schmid, G., Kässner, F., Uhlig, H. et al. Sirolimus treatment of severe PTEN hamartoma tumor syndrome: case report and in vitro studies. Pediatr Res 75, 527–534 (2014). https://doi.org/10.1038/pr.2013.246
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DOI: https://doi.org/10.1038/pr.2013.246
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